Antivenin (Micrurus fulvius)

(an tee VEN in mye KRU rus FUL vee us)

• Antivenin

Refer to adult dosing.

Frequency not defined.

Immediate reactions:

Immediate reactions may occur within 30 minutes and may start before needle is withdrawn. Symptoms include apprehension, collapse, cough, cyanosis, dyspnea, facial edema, flushing, laryngeal edema, pruritus, tongue edema, urticaria, vomiting.

Cardiovascular: Shock

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Delayed reactions:

Delayed reactions occur 5 to 24 days following administration. Symptoms include arthralgia, edema, fever, lymphadenopathy, malaise, nausea, urticaria, vomiting. Neurological symptoms (eg, amyotrophy, meningism, myasthenia, pain, and peripheral neuritis) may also occur.

Hypersensitivity: Serum sickness

Concerns related to adverse effects:

• Delayed serum sickness: Delayed serum sickness may occur 1 to 3 weeks from administration (especially when large doses used) even with a negative allergic history and absence of reaction to skin test.

• Horse serum hypersensitivity: Carefully review allergies and history of exposure to products containing horse serum. History of atopic sensitivity to horses may increase risk of immediate sensitivity reactions. Use with caution in patients with asthma, hay fever, or urticaria.

Concurrent drug therapy issues:

• Beta-blockers: Concomitant use with beta-blockers may prolong and increase the severity of acute anaphylaxis.

• Sedatives/opioids: Use sedatives with extreme caution; concomitant use with opioids or other analgesics that suppress respiration is contraindicated.

Other warnings/precautions:

• Appropriate use: North American coral snake envenomation: Do not administer prophylactically to asymptomatic patients. Clinicians should note that antivenin (Micrurus fulvius) does not neutralize venom of the Arizona or Sonoran coral snake (Micruroides euryoxanthus).

• Desensitization: A desensitization protocol is available if sensitivity tests are mildly or questionably positive to reduce risk of immediate severe hypersensitivity reaction. According to the manufacturer, desensitization should be performed when antivenin administration would be lifesaving; however, the risk of anaphylaxis should be weighed against the risks associated with delayed antivenin administration.

• Resuscitation precautions: All patients require close monitoring in a setting that has ready access to medications and equipment for resuscitation.

• Skin test: The manufacturer recommends that a skin test be performed prior to administration; however, the utility of skin tests to accurately identify patients at risk of early (anaphylactic) or late (serum sickness) hypersensitivity reactions to horse-derived antivenins has been questioned (Klaewsongkram 2009; WHO 2005). The absence of a skin hypersensitivity reaction does not exclude anaphylaxis or hypersensitivity following antivenin administration. False-negative rate for skin testing is 10% with similar agents. Conversely, hypersensitivity is not an absolute contraindication in a significantly envenomated patient.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber loss of strength and energy, flushing, anxiety, cough, shortness of breath, blue or gray skin discoloration, nausea, vomiting, passing out, enlarged lymph nodes, edema, joint pain, burning or numbness feeling, muscle weakness, or muscle pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

For persons with coral snake envenomations threatening life or limb, there are no contraindications to administration of Antivenin. However, administration to persons known to be allergic to horse serum, either by history or as a result of an appropriate sensitivity test, requires careful judgement and considerable experience in the use of antivenoms of equine origin. Healthcare providers must be prepared to manage severe, immediate allergic reactions (anaphylaxis) seen with Antivenins of equine origin. 8,9,10,11

Antivenin should never be administered prophylactically to asymptomatic patients. 12

IMPORTANT:  Before administration, read sections on " CONTRAINDICATIONS WARNINGS , PRECAUTIONS and Adverse Reactions ". Since the possibility of a severe immediate reaction (anaphylaxis) always exists whenever horse serum is administered, appropriate therapeutic agents, such as tourniquet, oxygen supply, epinephrine 1:1000, and another injectable pressor amine (NOT corticosteroids), must be ready for immediate use.

Start an intravenous drip of 250 to 500 ml of Sodium Chloride Injection, USP. If the results of appropriate tests have indicated the patient is not dangerously hypersensitive to horse serum, and depending on the nature and severity of the signs and symptoms of envenomation, administer the contents of 3 to 5 vials (30 to 50 ml) INTRAVENOUSLY by slow injection directly into the intravenous tubing or by adding to the reservoir bottle of the intravenous drip. (If added to reservoir bottle, mix by gentle swirling--DO NOT SHAKE.) In either case, the first 1 or 2 ml should be injected over a 3- to 5-minute period with careful observation of the patient for evidence of allergic reaction. If no signs or symptoms of anaphylaxis appear, continue the injection or intravenous infusion. The rate of delivery is regulated by the severity of signs and symptoms of envenomation and tolerance of Antivenin. However, until the equivalent of 30 to 50 ml of undiluted Antivenin has been given, administer at the maximum safe rate for intravenous fluids, based on body weight and general condition of the patient. For instance, if given by intravenous drip to a previously healthy adult, allow 250 or 500 ml to run in within 30 minutes; in small children, allow the first 100 ml to run in rapidly but then decrease to a rate not to exceed 4 ml per minute. Response to treatment may be rapid and dramatic. Observe the patient carefully and administer additional Antivenin intravenously as required.

According to the data reported by Fix and Minton 2 and cited above concerning venom yields obtained under artificial but probably physiological biting conditions, some envenomated patients may require administration of the contents of 10 or more vials to neutralize the venom dose injected by the biting snake if the entire venom load were delivered by the bite(s).

Snakes' mouths do not harbor Clostridium tetani. However, appropriate tetanus prophylaxis is indicated, since tetanus spores may be carried into the fang puncture wounds by dirt present on skin at time of bite or by nonsterile first-aid procedures.

A broad-spectrum antibiotic in adequate dosage is indicated if local tissue damage is evident.

Technique for Reconstituting the Dried Antivenin

Pry off the small metal disc in the cap over the diaphragms of the vials of Antivenin and diluent. Swab the exposed surface of the rubber diaphragms of both vials with an appropriate germicide. With a sterile 10 ml syringe and needle, withdraw the diluent (Sterile Water for Injection, USP) from the vial of diluent and insert the needle through the stopper of the vacuum-containing vial of Antivenin. The vacuum in the Antivenin vial will pull the diluent out of the syringe into the vial. However, delivery of 10 ml of diluent may not always exhaust the vacuum in the Antivenin vial. If all vacuum is not exhausted, reconstitution may be more difficult. Therefore, either disconnect the needle from the syringe and allow room air to be pulled into the Antivenin vial until all vacuum is released from the container or withdraw the syringe with attached needle from the vial, pull 10 ml of room air into the syringe and reinsert needle with attached syringe containing room air through stopper and repeat, if necessary, to release any remaining vacuum. At the first introduction of diluent into the vaccine vial, it is important for the needle to be pointed at the center of the lyophilized pellet of Antivenin so that the diluent stream will wet the pellet. If the diluent stream is not directed at the pellet but allowed to run down the inside wall of the vial, the pellet will float up and adhere to the stopper thereby rendering complete reconstitution much more difficult. Agitate by swirling, NOT by shaking, for 1 minute, at 5-minute intervals. Gentle agitation will hasten complete dissolution of the lyophilized Antivenin. Shaking causes foaming and if the diluent stream is not properly directed as described earlier, pieces of the pellet may get caught in the foam and will be very difficult to wet. Complete reconstitution usually requires at least 30 minutes.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The color of reconstituted Antivenin may vary from clear to slight yellowish or greenish.

Before each administration, gently swirl the vial to dissolve the contents.

Before any Antivenin is administered, an appropriate horse-serum sensitivity test must be done so that, in case administration of Antivenin is subsequently required, a decision on how to proceed will have been made (see PRECAUTIONS ).

Each package contains one vacuum vial to yield 10 ml of Antivenin (with preservatives: phenol 0.25% and thimerosal [mercury derivative] 0.005%).

Store original, unused (not reconstituted) vials between 2 and 8 °C (36 and 46 °F). Do not freeze.

Gently swirl the vial of reconstituted Antivenin before each administration.